177-lutetium-psma before stereotactic body radiotherapy for the treatment of oligorecurrent prostate cancer, the lunar study

Conditions: Oligometastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Adenocarcinoma; Stage IVB Prostate Cancer AJCC v8

Summary: this phase ii trial tests whether 177-lutetium-psma given before stereotactic body radiotherapy (sbrt) works to improve cancer control rate in patients with 1-5 prostate cancer tumors that have come back after prior treatment (oligorecurrent). radioactive drugs, such as 177-lutetium-psma, may carry radiation directly to tumor cells and not harm normal cells. sbrt uses special equipment to position a patient and deliver radiation to tumors with high precision. this method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. giving 177-lutetium-psma before sbrt may make the sbrt more effective.

primary objective: i. to assess progression-free survival for men with oligorecurrent prostate cancer after stereotactic body radiotherapy (sbrt) versus sbrt plus neoadjuvant lutetium lu-177 pnt2002 (177lu-pnt2002), with progression defined on the basis of prostate-specific membrane antigen positron emission tomography/computerized tomography (psma pet/ct) scans obtained at standard intervals (12 months and 24 months post-sbrt) or at the time of prostate-specific antigen (psa)-based biochemical progression, or initiation of salvage therapy or death. secondary objectives: i. to evaluate disease burden of disease (including local control of irradiated lesions and presence of other disease) on a psma pet/ct obtained 24 months after sbrt of sbrt versus sbrt + 177lu-pnt2002 in patients with oligometastatic disease who have not progressed by that point. ii. to assess physician-scored toxicity (common terminology criteria for adverse events version 5.0 \[ctcae v 5.0\]) of sbrt versus sbrt + 177lu-pnt2002 in patients with oligometastatic disease. iii. to assess patient-reported quality of life (based on the brief pain inventory scale) after sbrt versus sbrt + 177lu-pnt2002 in patients with oligometastatic disease. iv. to assess androgen deprivation therapy (adt)-free survival after sbrt versus sbrt + 177lu-pnt2002 in patients with oligometastatic disease. v. to determine local control of irradiated lesion at 12 months after sbrt versus sbrt + 177lu-pnt2002 in patients with oligometastatic disease (based on a scheduled psma-pet). vi. to assess time to locoregional progression, time to distant progression, time to new metastasis, and duration of response after sbrt versus sbrt + 177lu-pnt2002 in patients with oligometastatic disease (based on standard of care imaging). correlative objectives: i. to enumerate circulating tumor cells (ctcs) and circulating tumor deoxyribonucleic acid (ctdna) at baseline, 3 months, 6 months, and 12 months after sbrt. ii. to quantitatively sequence t-cell receptor (tcr) repertoires using peripheral blood monocytes at baseline, 3 months, 6 months, and 12 months after sbrt. iii. to perform radiomics analysis on psma pet/ct scans performed at +12 months (mo.), +24 months post-sbrt, or at time of progression. outline: patients are randomized to 1 of 2 arms. arm 1: beginning on day 1, patients undergo sbrt to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity. arm 2: patients receive 177lu-pnt2002 intravenously (iv) over 1-10 minutes on days -112 and -56 in the absence of disease progression or unacceptable toxicity. beginning on day 1, patients then undergo sbrt to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity. after completion of study treatment patients are followed up at 1, 3, 6, 9, and 12 months, then every 6 months until 60 months of total follow-up.

Eligibility criteria:
inclusion criteria: * oligorecurrent prostate cancer as determined by the presence of 1-5 asymptomatic lesions outside the prostate or prostate bed identified on psma pet/ct by local readers * age \>= 18 years * eastern cooperative oncology group (ecog) performance status =\< 2 * no indication for urgent or emergent radiation * histologic confirmation of prostate adenocarcinoma (histology from original treatment acceptable) * white blood cell count \>= 2.5 × 10\^9/l * platelets \>= 100 × 10\^9/l * hemoglobin \>= 9 g/dl * total bilirubin =\< 1.5 × institutional upper limit of normal (uln); or up to 3 × uln if known history of gilbert's syndrome * alanine aminotransferase or aspartate aminotransferase =\< 3.0 × uln or =\< 5.0 × uln for patients with liver metastases * serum creatinine =\ = 50 ml/min * serum albumin \> 3.0 g/dl * partner and patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration * ability to understand, and willingness to sign, the written informed consent exclusion criteria: * patients with neuroendocrine or small cell carcinoma of the prostate * patients with castrate-resistant disease (i.e., psa \> 0.5 ng/ml with serum testosterone \< 150 ng/dl) * patients who received androgen deprivation therapy within 6 months of trial enrollment * concurrent systemic therapy for a solid organ malignancy * spinal cord compression * inability to lie flat * known hypersensitivity to components of 177lu-pnt2002 * serum creatinine \> 1.5 × uln or creatinine clearance \< 50 ml/min * total bilirubin \> 1.5 × uln or \> 3.0 × uln if known history of gilbert's syndrome * alanine aminotransferase or aspartate aminotransferase \> 3 × uln (or 5 × uln for patients with known liver metastases) * de novo oligometastatic disease